Figure 3. The DNA-binding surface and contacts formed by one subunit of the I-CreI homing endonuclease (from Figure 2c).

a: An antiparallel β-sheet structure presents a group of broadly distributed side chains to the major groove of the DNA target site, where they make a variety of specific and nonspecific contacts. b: A schematic of the contacts made by the structure shown in panel a. Hydrogen-bond acceptor and donor positions on each basepair are shown with concave and convex features on each base; direct contacts are shown with red arrows; water-mediated contacts are shown with blue arrows and blue spheres, which denote the water molecules in the crystal structure). Individual basepairs display a wide variation in the total number of contacts to protein atoms; this variation correlates approximately with the fidelity of recognition that is displayed at each position. Additional specificity is derived by indirect exploitation of sequence-specific conformational preferences of the DNA target, which is often bent as part of endonuclease binding and cleavage.